A formal total synthesis of (-)-FR901483, using a tandem cationic aza-cope rearrangement/Mannich cyclization approach

被引:60
作者
Brummond, KM [1 ]
Hong, SP [1 ]
机构
[1] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA
关键词
D O I
10.1021/jo0483567
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
A formal total synthesis of the immunosuppressant FR901483 has been accomplished. The key step in the synthesis utilizes a tandem cationic aza-Cope rearrangement/Mannich cyclization reaction for accessing the unprecedented bridging tricyclic azaspirane substructure of this compound. The tandem reaction proceeds through a bridgehead iminium ion, a functionality that has rarely been explored in the context of natural product syntheses. Improved stereoselectivity was observed in an aldol reaction when using a Boc-protected amino aldehyde and zinc chloride as an additive. A stereoselective epimerization of the aldehyde-containing stereocenter was achieved with L-phenylalanine upon completion of the Mannich cyclization. Finally, this synthesis is the only one to date that controls the stereochemistry of the oxygen-bearing stereocenters. All other synthetic routes required late stage adjustments to at least one of these stereocenters.
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页码:907 / 916
页数:10
相关论文
共 41 条
[1]  
[Anonymous], [No title captured]
[2]   STEREOSPECIFIC FORMATION OF ENOLATES FROM REACTION OF UNSYMMETRICAL KETENES AND ORGANO-LITHIUM REAGENTS [J].
BAIGRIE, LM ;
SEIKLAY, HR ;
TIDWELL, TT .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1985, 107 (19) :5391-5396
[3]   A new synthetic entry to the tricyclic skeleton of FR901483 by palladium-catalyzed cyclization of vinyl bromides with ketone enolates [J].
Bonjoch, J ;
Diaba, F ;
Puigbó, G ;
Peidró, E ;
Solé, D .
TETRAHEDRON LETTERS, 2003, 44 (46) :8387-8390
[4]   Synthesis and biological evaluation of a conformationally free seco-analogue of the immunosuppressant FR901483 [J].
Bonjoch, J ;
Diaba, F ;
Puigbó, G ;
Solé, D ;
Segarra, V ;
Santamaría, L ;
Beleta, J ;
Ryder, H ;
Palacios, JM .
BIOORGANIC & MEDICINAL CHEMISTRY, 1999, 7 (12) :2891-2897
[5]   Synthesis of spirolactams from tyrosine amides and related substances [J].
Braun, NA ;
Ciufolini, MA ;
Peters, K ;
Peters, EM .
TETRAHEDRON LETTERS, 1998, 39 (26) :4667-4670
[6]   Tandem cationic aza-Cope rearrangement-Mannich cyclization approach to the core structure of FR901483 via a bridgehead iminium ion [J].
Brummond, KM ;
Lu, JL .
ORGANIC LETTERS, 2001, 3 (09) :1347-1349
[7]  
Czernecki S., 1976, TETRAHEDRON LETT, V17, P3535
[8]   SYNTHESIS APPLICATIONS OF CATIONIC AZA-COPE REARRANGEMENTS .27. ENANTIOSELECTIVE TOTAL SYNTHESIS OF EITHER ENANTIOMER OF THE ANTIFUNGAL ANTIBIOTIC PREUSSIN (L-657,398) FROM (S)-PHENYLALANINE [J].
DENG, W ;
OVERMAN, LE .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1994, 116 (25) :11241-11250
[9]   SYNTHESIS OF AZAMODIFIED ADAMANTANE DERIVATIVES VIA BRIDGEHEAD IMINES AND BRIDGE IMINES - A NEW ASPECT IN THE CHEMISTRY OF HETEROADAMANTANE DERIVATIVES [J].
EGUCHI, S ;
OKANO, T ;
TAKEUCHI, H .
HETEROCYCLES, 1987, 26 (12) :3265-3284
[10]   A NEW SYNTHESIS OF (-)-ANISOMYCIN OR (+)-ANISOMYCIN STARTING FROM D-TYROSINE OR L-TYROSINE [J].
JEGHAM, S ;
DAS, BC .
TETRAHEDRON LETTERS, 1988, 29 (35) :4419-4422